We evaluated the impact on alcohol intake and blood alcohol concentration (BAC) of a multi-level structural intervention to increase the availability of free water, coupled with messaging on pacing alcohol intake and normative feedback of blood alcohol concentration in a convenience sample of gay bars in San Francisco. Participants (n = 1,293) were recruited among exiting patrons of four gay bars (two intervention bars and two control bars). Participants were surveyed on alcohol intake and BAC was measured by breathalyzer. Prior to the intervention there were no significant differences in baseline alcohol measures between intervention and control bars. Post-intervention there were significant differences on objective and subjective measures of alcohol consumption: 30% of intervention bar participants had BAC% levels over the legal driving limit (0.08%) compared to 43% of control bar participants, p < 0.0001 and 78% of intervention bar participants were above the AUDIT-C cut-off for hazardous drinking compared to 87% in control bars, p < 0.001.

The original version of this article contains an omission in the list of authors for Dr. Adam W. Carrico. The corrected authors list for the article is given in this erratum.

Background

Diminished growth is highly prevalent among HIV-infected children and might be improved by antiretroviral therapy (ART). We examined growth recovery in a rural Ugandan cohort of HIV-infected children randomized to lopinavir/ritonavir (LPV/r) or non nucleoside reverse transcription inhibitor-based ART.

Methods

HIV-infected children 2 months to 6 years of age were randomized to LPV/r- or non nucleoside reverse transcription inhibitor-based ART. Changes in weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height Z-scores for 24 months were evaluated using generalized linear repeated measures models. Recovery from being underweight (WAZ<-2), stunted (HAZ<-2) and wasted (weight-for-height <-2) to Z-scores greater than -2 was also compared by arm using Kaplan-Meier survival and Cox proportional hazard modeling.

Results

A total of 129 children with median age of 3 years initiated therapy; 64 received LPV/r-based and 65 non nucleoside reverse transcription inhibitor-based ART (nevirapine: 36 and efavirenz: 29). The median (interquartile range) difference in growth measures between baseline and 24 months for LPV/r (n = 45) versus non nucleoside reverse transcription inhibitor-based therapy (n = 40) were as follows: WAZ, 0.47 (0.10, 1.62) versus 0.53 (0.03, 1.14) (P = 0.59) and HAZ, median 1.55 (0.78, 1.86) versus 1.19 (0.62, 1.65) (P = 0.23), respectively. ART regimen was not predictive of change in WAZ (β: -0.02, 95% confidence interval: -0.25, 0.20) or HAZ (β: 0.05, 95% confidence interval: -0.10, 0.19). The presence of confirmed virologic failure was not associated with growth.

Conclusions

Most ART-naive children experienced recovery of both WAZ and HAZ over the 24 months after ART initiation, with no significant difference between those receiving LPV/r versus non nucleoside reverse transcriptase inhibitor-based ART. However, the persistence of median Z-scores below 0 underscores the need for additional strategies to improve growth outcomes in HIV+ African children.

As human immunodeficiency virus (HIV)-infected women gain access to combination antiretroviral therapy throughout sub-Saharan Africa, a growing number of infants are being born HIV-exposed but uninfected. Data about neonatal mortality and the impact of premature delivery, in this population are limited. We describe the 28-day mortality outcomes in a cohort of HIV-exposed infants who had ultrasound-confirmed gestational age in rural Uganda. There were 13 deaths among 351 infants, including 9 deaths in the perinatal period. Premature delivery was a strong predictor of mortality. The prevention of HIV transmission to infants is now possible in rural low-resource settings but the frequency of neonatal death among HIV-exposed infants remains extremely high, calling for new comprehensive interventions to reduce mortality in this growing population.

Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. Eighty percent of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m(2) . Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV -33%, EFV -15%, ritonavir -17%) compared to well-nourished controls (P < 0.001), attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% (P < 0.001), whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure (P < 0.001), explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority.

Objective

Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4⁺ cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda.

Design

Randomized clinical trial.

Methods

We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naive pregnant women at 12-28 weeks gestation and any CD4⁺ cell count were randomized. ART was provided and participants were counseled to breastfeed for 1 year postpartum.

Results

The median age of the 389 study participants was 29 years; median CD4⁺ cell count was 370 cells/μl. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm (P < 0.001). At 48 weeks postpartum, 91.0% of women on efavirenz and 88.4% on lopinavir/ritonavir had viral suppression (P = 0.49). Grade 1 or 2 gastrointestinal adverse events were higher among women on lopinavir/ritonavir versus efavirenz. Only two infants acquired HIV (both in the lopinavir/ritonavir arm), and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz) (P = 0.10).

Conclusion

Virologic suppression at delivery was higher with an efavirenz versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through 1 year postpartum and the risk of transmission to infants was low.

Efficient ways to identify children with HIV in the context of universal test-and-treat policies are needed. We evaluated a hybrid testing strategy combining mobile community and home-based HIV testing in 87,700 children across 32 rural communities in 2 East African countries. This approach resulted in 81% testing coverage of at-risk children and doubled the number of children diagnosed with HIV.

Objective

Hair concentrations are a noninvasive measure of cumulative antiretroviral exposure and the strongest predictor of viral suppression in large cohorts of nonpregnant patients. We examined hair concentrations of antiretrovirals in relation to virologic outcomes in pregnant and breastfeeding women for the first time.

Design and methods

The Prevention of Malaria and HIV Disease in Tororo trial (NCT00993031) enrolled HIV-infected pregnant Ugandan women at 12-28 weeks gestation who were randomized to lopinavir or efavirenz-based antiretroviral therapy (ART). Small hair samples were collected at 30-34 weeks gestation and 10-25 weeks postpartum. Efavirenz and lopinavir hair concentrations were measured via liquid chromatography/tandem mass spectrometry. Multivariate logistic regression models examined predictors of viral suppression (HIV-1 RNA ≤400 copies/ml) at delivery and 24 weeks postpartum.

Results

Among 325 women, median CD4 cell count was 366 cells/μl (interquartile range 270-488) at ART initiation. Mean self-reported 3-day adherence was greater than 97% in each arm. Viral suppression was achieved by 98.0% (efavirenz) and 87.4% (lopinavir) at delivery. At 24 weeks postpartum, 92.5% (efavirenz) and 90.6% (lopinavir) achieved viral suppression; 88% of women were breastfeeding. In multivariate models including self-reported adherence and pretreatment HIV-1 RNA, antiretroviral hair concentrations were the strongest predictor of viral suppression at delivery [efavirenz: adjusted odds ratio (aOR) 1.86 per doubling in concentration, 95% confidence interval (CI) 1.14-3.1, P = 0.013; lopinavir: aOR 1.90, 95% CI 1.33-2.7, P = 0.0004] and 24 weeks postpartum (efavirenz: aOR 1.81, 95% CI 1.22-2.7, P = 0.003; lopinavir: aOR 1.53, 95% CI 1.05-2.2, P = 0.026).

Conclusion

Antiretroviral hair concentrations represent an innovative tool that strongly predicts viral suppression among HIV-infected childbearing women during the critical periods of delivery and breastfeeding.